Trends in Cell Biology

Glia maturation factor (GMF) has recently been established as a regulator of the actin cytoskeleton with a unique role in remodeling actin network architecture. Conserved from yeast to mammals, GMF is one of five members of the ADF-H family of actin regulatory proteins, which includes ADF/cofilin, Abp1/Drebrin, Twinfilin, and Coactosin. GMF does not bind actin, but instead binds the Arp2/3 complex with high affinity. Through this association, GMF catalyzes the debranching of actin filament networks and inhibits actin nucleation by Arp2/3 complex...

Recent studies involving induced pluripotent stem cell (iPSC) reprogramming in mice and monocyte-to-macrophage differentiation in humans have revealed a role for the transcription factor (TF) activator protein 1 (AP-1) in chromatin accessibility. Enhancer selection may be determined not only by cell type-specific sets of TFs but also by broadly expressed ones like AP-1.

Damaged cells at risk of neoplastic transformation can be neutralized by apoptosis or engagement of the senescence program, which induces permanent cell-cycle arrest and a bioactive secretome that is implicated in tumor immunosurveillance. While from an evolutionary perspective senescence is beneficial in that it protects against malignancies, the accumulation of senescent cells in tissues and organs with aging and at sites of various pathologies is largely detrimental. Because induction of senescence in cancer cells is emerging as a therapeutic concept, it will be important to consider these detrimental effects, including tumor-promoting properties that may drive the formation of secondary tumors or cancer relapse...

Enhancers are distally located genomic cis-regulatory elements that integrate spatiotemporal cues to coordinate gene expression in a tissue-specific manner during metazoan development. Enhancer function depends on a combination of bound transcription factors and cofactors that regulate local chromatin structure, as well as on the topological interactions that are necessary for their activity. Numerous genome-wide studies concur that the vast majority of disease-associated variations occur within non-coding genomic sequences, in other words the 'cis-regulome', and this underscores their relevance for human health...

Cellular communication relies on fusion of secretory vesicles with the plasma membrane, following dynamic events that change the micro- and nanoscale environment of the approaching vesicles in the vicinity of docking sites. Visualization of fine cortical actin network structures and their interactions with vesicle and plasma membrane has recently been facilitated by the development of new imaging technologies. Consequently, a greater understanding is emerging of the role of the cortical actin network on controlling secretory vesicles as they undergo docking, priming, and fusion in exocytic hot spots...

Metastasis to distant organs is a predictor of poor prognosis. Therefore, it is of paramount importance to understand the mechanisms that impinge on the different steps of the metastatic cascade. Recent work has revealed that particular metabolic pathways are rewired in cancer cells to support their transition through the metastatic cascade, resulting in the formation of secondary tumors in distant organs. Indeed, metabolic rewiring induces signaling pathways during initial cancer invasion, circulating cancer cells depend on enhanced antioxidant defenses, and cancer cells colonizing a distant organ require increased ATP production...

Genetic studies have demonstrated that conditional ablation of core autophagy genes in the neural lineage leads to progressive neurodegeneration, indicating that this catabolic pathway is indispensable for neuronal maintenance. However, accumulating evidence also indicates that autophagy is not merely a housekeeping process. Instead, autophagy may be dynamically regulated in different neuronal compartments and dictate the turnover of selected cargo in a time- and space-dependent manner and thus contribute to specialized neuronal functions...

Endothelial cells can sense and respond to blood flow forces and signals, but the exact mechanisms employed remain poorly understood. A recent study describes how low-flow forces are sensed by primary cilia during development of the retinal vasculature, which sensitizes endothelial cells to BMP signaling.

Vitamin C is an essential dietary requirement for humans. In addition to its known role as an antioxidant, vitamin C is a cofactor for Fe2+ - and α-ketoglutarate-dependent dioxygenases (Fe2+ /α-KGDDs) which comprise a large number of diverse enzymes, including collagen prolyl hydroxylases and epigenetic regulators of histone and DNA methylation. Vitamin C can modulate embryonic stem cell (ESC) function, enhance reprogramming of fibroblasts to induced pluripotent stem cells (iPSCs), and hinder the aberrant self-renewal of hematopoietic stem cells (HSCs) through its ability to enhance the activity of either Jumonji C (JmjC) domain-containing histone demethylases or ten-eleven translocation (TET) DNA hydroxylases...

The nucleolus is a prominent membraneless organelle residing within the nucleus. The nucleolus has been regarded as a housekeeping structure mainly known for its role in ribosomal RNA (rRNA) production and ribosome assembly. However, accumulating evidence has revealed its functions in numerous cellular processes that control organismal physiology, thereby taking the nucleolus much beyond its conventional role in ribosome biogenesis. Perturbations in nucleolar functions have been associated with severe diseases such as cancer and progeria...

In mitotic cells, cellular senescence is a permanent state of G1 arrest, that may have evolved in parallel to apoptosis, to limit proliferation of damaged cells and oncogenesis. Recent studies have suggested that postmitotic cells are also capable of entering a state of senescence, although the repercussions of postmitotic cellular senescence (PoMiCS) on tissue health and function are currently ill-defined. In tissues made largely of post-mitotic cells, it is evolutionary advantageous to preserve cellular integrity and cellular senescence of post-mitotic cells may prevent stressor-induced tissue degeneration and promote tissue repair...

Conjugation of ubiquitin onto proteins generates a degradation signal or exerts degradation-independent regulatory functions. Ubiquitylation is governed by the antagonistic action of ubiquitin ligases and deubiquitylating enzymes (DUBs). Several recent publications illustrate a balanced interplay of ligases and DUBs at signaling hubs that are central to longevity and protein homeostasis (proteostasis). In addition, stress-induced alterations of ubiquitin conjugation are emerging as key events that drive aging and contribute to the pathology of age-related diseases...

How the behavior of cells in living tissues is orchestrated according to tissue needs, size, and developmental stage is still poorly understood. Advances in these directions are essential to understand morphogenesis, 'self-organization' phenomena, to build new tissues for regenerative medicine or to reverse the changes in deranged organs, such as in cancer or in genetic disorders. This review outlines a new scenario by which the crosstalk between the Yes-associated protein/transcriptional coactivator with PDZ-binding motif (YAP/TAZ) transcription factors and Notch signaling influences cell self-renewal, stem cell differentiation, cell fate decisions, epithelial-stromal interactions, inflammation, morphogenesis, and large-scale gene oscillations...

Self-organization guides robust, spatiotemporally ordered formation of complex tissues and ultimately whole organisms. While products of gene expression serve as building blocks of living matter, how these interact to give rise to tissues of distinct patterns and function remains a central question in biology. Tissue self-organization relies on dynamic interactions between constituents spanning a range of spatiotemporal scales with tuneable chemical and mechanical parameters. This review highlights recent studies dissecting mechanisms of these interactions...

Cellular compartments and organelles organize biological matter. Most well-known organelles are separated by a membrane boundary from their surrounding milieu. There are also many so-called membraneless organelles and recent studies suggest that these organelles, which are supramolecular assemblies of proteins and RNA molecules, form via protein phase separation. Recent discoveries have shed light on the molecular properties, formation, regulation, and function of membraneless organelles. A combination of techniques from cell biology, biophysics, physical chemistry, structural biology, and bioinformatics are starting to help establish the molecular principles of an emerging field, thus paving the way for exciting discoveries, including novel therapeutic approaches for the treatment of age-related disorders...

Interorganellar contacts are increasingly recognized as central to the control of cellular behavior. These contacts, which typically involve a small fraction of the endomembrane surface, are local communication hubs that resemble synapses. We propose the term contactology to denote the analysis of interorganellar contacts. Endoplasmic reticulum (ER) contacts with mitochondria were recognized several decades ago; major roles in ion and lipid transfer, signaling, and membrane dynamics have been established, while others continue to emerge...

Microtubule organization has a crucial role in regulating cell architecture. The geometry of microtubule arrays strongly depends on the distribution of sites responsible for microtubule nucleation and minus-end attachment. In cycling animal cells, the centrosome often represents a dominant microtubule-organizing center (MTOC). However, even in cells with a radial microtubule system, many microtubules are not anchored at the centrosome, but are instead linked to the Golgi apparatus or other structures. Non-centrosomal microtubules predominate in many types of differentiated cell and in mitotic spindles...

To battle adverse internal and external conditions and maintain homeostasis, diploid organisms employ various cellular processes, such as proliferation and apoptosis. In some tissues, an alternative mechanism, endoreplication, is employed toward similar goals. Endoreplication is an evolutionarily conserved cell cycle program during which cells replicate their genomes without division, resulting in polyploid cells. Importantly, endoreplication is reported to be indispensable for normal development and organ formation across various organisms, from fungi to humans...